Mentoring in Patient-Oriented and Translational HFpEF Research

以患者为导向的转化性 HFpEF 研究的指导

• 批准号: 10040036
• 负责人: Jennifer E Ho
• 金额: $ 12.35万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10040036
• 关键词: Address; Adverse event; Affect; Analytical Chemistry; Area; Attention; Award; Biochemical; Bioinformatics; Blood Vessels; Cardiopulmonary; Cardiopulmonary Physiology; Cardiovascular system; Classification; Clinical; Clinical Investigator; Clinical Research; Clostridium perfringens epsilon toxin; Collaborations; Communities; Complement; Complex; Coupled; Coupling; Development; EFRAC; Environment; Exercise; Exercise Physiology; Exercise Test; Fellowship Program; Foundations; Functional disorder; Funding; Future; General Hospitals; Goals; Heart; Heart failure; Hospitals; Human; Individual; Inflammation; Inflammatory; Inflammatory Response; Infrastructure; Insulin Resistance; Interdisciplinary Study; International; Investigation; Knowledge; Laboratories; Lead; Learning; Link; Lung; Massachusetts; Medicine; Mentors; Mentorship; Metabolic Diseases; Metabolic dysfunction; Mid-Career Clinical Scientist Award (K24); Monitor; Morbidity - disease rate; Obesity; Organ; Outcome; Pathogenesis; Pathway interactions; Patients; Phenotype; Physiological; Prevention therapy; Productivity; Prospective Studies; Public Health; Public Health Schools; Pulmonary Hypertension; Research; Research Methodology; Research Personnel; Research Support; Research Training; Resources; Right Ventricular Function; Risk Factors; Role; Sampling; Seminal; Sex Differences; Therapeutic; Training; Translational Research; United States National Institutes of Health; Universities; Ventricular; Woman; Work; adjudicate; base; cardiometabolism; career; career development; clinical epidemiology; clinical heterogeneity; cohort; disease phenotype; disorder prevention; education resources; effective therapy; hemodynamics; interest; men; mortality; optimal treatments; outcome prediction; patient oriented; patient oriented research; preservation; programs; prospective; public health relevance; recruit; training opportunity; translational research program; translational study

Project Summary/Abstract Heart failure (HF) is a major public health problem worldwide, and half of patients presenting with HF have preserved (HFpEF), rather than reduced ejection fraction. However, HFpEF remains a therapeutic challenge, given current limited understanding of causal and contributing factors, and clinical heterogeneity within HFpEF subphenotypes. The central goal of the candidate's research work is to use clinical and translational research approaches to better understand mechanisms and contributors to human HFpEF and its subphenotypes. One focus in the laboratory has been to study the role of obesity, which is thought to induce a systemic pro- inflammatory state that, in turn, drives cardiovascular dysfunction and remodeling leading to HFpEF. The candidate is a heart failure cardiologist with a research focus on HFpEF and a long-standing track record of successful mentoring. Current work includes a multi-cohort effort to examine upstream regulators of systemic inflammation in HFpEF. This is complemented by a prospective ongoing study examining the role of obesity and insulin-resistance in HFpEF-associated pulmonary hypertension. The overarching goals of this proposal are to provide the candidate with the crucial long-term support to enable the ongoing reduction from clinical and administrative commitments, and to expand training opportunities for mentees interested in clinical and translational patient-oriented heart failure research. This application will support the candidate in creating unique training opportunities by leveraging ongoing funded efforts to enable new patient-oriented studies led by mentees. In Aim 1, we will investigate sex differences in inflammatory profiles in HFpEF in order to better understand why men and women with HFpEF display distinct disease phenotypes. In Aim 2, we will examine obesity and metabolic dysfunction as determinants of right ventricular function, an important predictor of outcomes in HFpEF. These research opportunities within the candidate's multidisciplinary research program, coupled with a vibrant scientific community and extensive educational resources at Massachusetts General Hospital and Harvard University will create an unparalleled environment for trainees pursuing a career in patient-oriented research. Ultimately, we hope this proposal will support the development and mentoring of new clinical investigators in heart failure research, and lay the foundation for future investigations focused on disease prevention and optimal therapies in HFpEF.

项目概要/摘要 心力衰竭（HF）是世界范围内的一个主要公共卫生问题，一半的心力衰竭患者患有心力衰竭。 保留（HFpEF），而不是降低射血分数。然而，HFpEF 仍然是一个治疗挑战， 鉴于目前对 HFpEF 的因果因素和影响因素以及临床异质性的了解有限 亚表型。候选人研究工作的中心目标是利用临床和转化研究 更好地了解人类 HFpEF 及其亚表型的机制和贡献者的方法。一 实验室的重点是研究肥胖的作用，肥胖被认为会诱发系统性促 炎症状态反过来会导致心血管功能障碍和重塑，从而导致 HFpEF。 候选人是一位心力衰竭心脏病专家，主要研究 HFpEF 并拥有长期的研究成果 成功指导的记录。目前的工作包括多方努力检查上游监管机构 HFpEF 中的全身炎症。一项正在进行的前瞻性研究对此进行了补充，该研究检查了 HFpEF 相关肺动脉高压中的肥胖和胰岛素抵抗。本次活动的总体目标 建议的目的是为候选人提供关键的长期支持，以实现持续减少 临床和行政承诺，并扩大对临床感兴趣的学员的培训机会 以及以患者为中心的转化性心力衰竭研究。该应用程序将支持候选人创建 通过利用持续资助的努力来实现以患者为主导的新研究，提供独特的培训机会 由受训者。在目标 1 中，我们将研究 HFpEF 炎症特征的性别差异，以便更好地 了解为什么患有 HFpEF 的男性和女性表现出不同的疾病表型。在目标 2 中，我们将检查 肥胖和代谢功能障碍是右心室功能的决定因素，是右心室功能的重要预测因素 HFpEF 的结果。候选人的多学科研究计划中的这些研究机会， 加上马萨诸塞州综合医院充满活力的科学界和广泛的教育资源 医院和哈佛大学将为学员在该领域的职业生涯创造无与伦比的环境 以患者为导向的研究。最终，我们希望该提案能够支持开发和指导 心力衰竭研究的新临床研究人员，并为未来的研究奠定基础 HFpEF 的疾病预防和最佳治疗。